The structures of many polyketide-derived natural products that have been elucidated in recent years often exhibit long sequence of stereogenic centers in which hydroxy-substituted secondary carbon atoms alternate with tertiary carbon atoms. 1 This proposal is focused on the stereoselective construction of the structural ensemble (1) with three directly adjacent chiral centers. An efficient construction of this ensemble will provide easy access to man biologically active compounds, such as erythronolide, rifamycin, and FK-506. This proposal has three major considerations: 1) Double asymmetric synthesis involving homochiral alpha-(alkoxyallyl)stannanes and alpha- chiral aldehydes; (2) diastereofacial selective functionalization of the enol either adducts obtained from first stage of study; and (3) applications of the new chemistry developed in this project to the total synthesis of biologically significant natural products.